NEW ORLEANS – A decline in levels of anti-müllerian hormone as women approach menopause – a phenomenon dubbed ovarian decline – appears associated with clinical disability and brain atrophy in women with multiple sclerosis, according to the findings of a study of more than 400 women with multiple sclerosis followed up for a decade.
This “accumulation of disability” may explain the often rapid transition from a benign disease course to secondary progressive multiple sclerosis (MS) in women as they approach menopause, Dr. Jennifer S. Graves reported at a meeting held by at the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Jennifer S. Graves
Earlier in life, females often have a more benign initial course of MS than males. The mean age of onset of primary progressive MS and secondary progressive MS are both approximately 45 years. The mean age of menopause is 51 years. Ovarian aging involves up to a 10-year period of decline in ovarian function. After age 50, “women catch up in terms of disability with males” with MS, said Dr. Graves of the University of California, San Francisco. One explanation could be that ovarian aging contributes to the development of progressive disease.
The objective was to determine if ovarian decline as measured by the levels of anti-müllerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS. The cohort of 412 female patients with MS (mean age, 43 years) was from the UCSF EPIC (Expression, Proteomics, Imaging, Clinical) study, which has followed more than 500 people with MS since 2004 with the aim of identifying factors that drive the disease. Also included were 180 healthy controls with the exact same mean age. AMH levels were measured using an ultrasensitive enzyme-linked immunosorbent assay at baseline and at years 3, 5, 8, 9, and 10. Brain magnetic resonance imaging data also were acquired.
When the data were adjusted for chronologic age, women with MS and healthy controls displayed similar AMH levels (P = .97), implying a normal follicular reserve and rate of ovarian decline in those with MS. White matter volume was associated with AMH levels at baseline (P = .047). The association did not persist when adjusted for age as well as disease duration and body mass index (P = .24), while ovarian reserve was associated with normalized gray matter volume (P = .049) and MS functional composite z scores (P = .036) at baseline. Scrutiny of the follow-up period revealed that a twofold decrease in AMH was associated with a 1.85-mm3 decrease in gray matter volume (P = .060) in MS patients. Almost a third of the MS patients had undetectable levels of AMH, which was associated with a 0.60-point higher expanded disability status scale score (P =.039)
The results support the hypothesized association of ovarian decline with increased severity of MS. Furthermore, AMH may be a useful biomarker of MS progression, said Dr. Graves. “The advantage of this biomarker would be that it captures biological activity in women in their 40s, and so could let you know of imminent change.”
Validation of the findings needs to be done.
The study was funded by the National Institutes of Health, National MS Society, Race to Erase MS, Foundation for the Cedars-Sinai Medical Center, Biogen, and Genentech. Dr. Graves had no relevant financial disclosures.